TSPY1 Copy Number Variation Influences Spermatogenesis and Shows Differences among Y Lineages

Abstract

TSPY copy number variation significantly influences spermatogenic efficiency. Low TSPY1 copy number is a new risk factor for male infertility with potential clinical consequences.

Male infertility: Pathogenesis and clinical diagnosis

“…Up to now only two CNVs have been correlated to infertility: i) AZFc gene dosage variation due to complete/partial removal or duplication of multicopy AZFc genes; ii) TSPY1 copy number variation on Yp. 78 Apart from few exceptions, such as central hypogonadism and some post-testicular forms, the only available treatment option for the large majority of male factor infertility is medically-assisted reproductive technology (ART), especially in vitro fertilization (IVF) or ICSI. 79,80 However, ART is a symptomatic therapy which does not address the underlying cause for infertility with the risk of transmitting both identified and not yet identified genetic anomalies.…”

The Y chromosome-linked copy number variations and male fertility

“…Indeed, crucial for a reliable analysis is the TSPY1 copy number variation susceptibility to stratification biases. As a matter of fact, significantly different means of TSPY1 copy number were found among different Y haplogroups (46,53), highlighting the importance of Y haplogroups-matching between cases and controls. The only available study to date in which cases and controls were matched for Y hgr distribution has been performed in the Italian population by our group.…”

“…During the last years, Y-linked copy number variation analyses have been extended to the short arm of the Y chromosome which contains a TSPY1 gene array with variable number of TSPY1 copies (46,47). The TSPY1 belongs to a protein superfamily comprising SET and NAP, which are activating factors of the replication process.…”

“…The only available study to date in which cases and controls were matched for Y hgr distribution has been performed in the Italian population by our group. The method used for the detection of TSPY1 copy number was validated against pulsedfield gel electrophoresis (the gold standard method) (46). The initially published study population has been recently enlarged and previous results confirmed i.e.…”

Sequence Recombination in Exon 1 of the Tspy Gene in Men With Impaired Fertility

“…The relative number of copies is higher in infertile men, with the exception of the AZFa deletion case 27 . Giachini et al 34 , found that the TSPY gene copy number affects spermatogenesis and that low copy number is a factor contributing to male infertility. On the other hand, Nickkholgh et al 35 argue that there is no correlation between impaired spermatogenesis and the TSPY gene copy number.…”